Publications by authors named "James Brandful"

9 Publications

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Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana.

Medicine (Baltimore) 2019 Feb;98(6):e14313

Virology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences.

Antiretroviral therapy (ART) and drug resistance studies worldwide have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1). As a result, there is limited information on ART and drug resistance in HIV-2 patients. In Ghana, the HIV epidemic is characterized by the domination of HIV-1, with cocirculating HIV-2. We, therefore, sought to determine viral load and drug resistance mutations in HIV-2 patients to inform the clinical management of such individuals in Ghana.We used purposive sampling to collect blood from 16 consented patients, confirmed as HIV-2 or HIV-1/2 dual infections by serology. A 2-step real-time RT-PCR assay was used to determine plasma HIV-2 RNA viral loads. For drug resistance testing, nucleic acids were extracted from plasma and peripheral blood mononuclear cells. The reverse transcriptase and protease genes of HIV-2 were amplified, sequenced and analyzed for drug resistance mutations and HIV-2 group.HIV-2 viral load was detected in 9 of 16 patients. Six of these had quantifiable viral loads (range: 2.62-5.45 log IU/mL) while 3 had viral loads below the limit of quantification. Sequences were generated from 7 out of 16 samples. Five of these were classified as HIV-2 group B and 2 as HIV-2 group A. HIV-2 drug resistance mutations (M184V, K65R, Y115F) were identified in 1 patient.This study is the first to report HIV-2 viral load and drug resistance mutations in HIV-2 strains from Ghana. The results indicate the need for continuous monitoring of drug resistance among HIV-2- infected patients to improve their clinical management.
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http://dx.doi.org/10.1097/MD.0000000000014313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380870PMC
February 2019

Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana.

J Med Microbiol 2017 Nov 25;66(11):1663-1672. Epub 2017 Oct 25.

Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.

Purpose: There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana.

Methodology: A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART. HIV viral load (VL) and CD4 T-cell counts were measured. The pol gene sequences were analysed for genotypic resistance by an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were analysed in detail.Results/Key findings. A total of 33 subjects were studied. Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10 (41.7 %) viruses possessed at least one mutation conferring resistance to nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two-class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1 subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique HIV-1 recombinant forms with CRF02_AG/A3 mosaic.

Conclusion: HIV-1 shows high genetic diversity and on-going viral genetic recombination in the study region. Nearly 42 % of the patients studied harboured a drug-resistant virus. The study underscores the need for continued surveillance of HIV-1 subtype diversity; and of drug-resistance patterns to guide selection of second-line regimens in northern Ghana.
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http://dx.doi.org/10.1099/jmm.0.000621DOI Listing
November 2017

H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa.

Genome Res 2016 Feb 1;26(2):271-7. Epub 2015 Dec 1.

University of the Free State, Bloemfontein, South Africa 9300;

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.
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http://dx.doi.org/10.1101/gr.196295.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728379PMC
February 2016

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus.

Biochem Biophys Res Commun 2015 Apr 26;459(2):288-293. Epub 2015 Feb 26.

Tokyo Medical and Dental University, Japan. Electronic address:

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.
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http://dx.doi.org/10.1016/j.bbrc.2015.02.102DOI Listing
April 2015

A perpetual source of DNA or something really different: ethical issues in the creation of cell lines for African genomics research.

BMC Med Ethics 2014 Aug 7;15:60. Epub 2014 Aug 7.

Department of Medicine, University of Cape Town, Office J52-16, UCT Centre for Clinical Research, Old Main Building, Groote Schuur Hospital, Observatory, 7925 Cape Town, South Africa.

Background: The rise of genomic studies in Africa - not least due to projects funded under H3Africa - is associated with the development of a small number of biorepositories across Africa. For the ultimate success of these biorepositories, the creation of cell lines including those from selected H3Africa samples would be beneficial. In this paper, we map ethical challenges in the creation of cell lines.

Discussion: The first challenge we identified relates to the moral status of cells living in culture. There is no doubt that cells in culture are alive, and the question is how this characteristic is relevant to ethical decision-making. The second challenge relates to the fact that cells in culture are a source of cell products and mitochondrial DNA. In combination with other technologies, cells in culture could also be used to grow human tissue. Whilst on the one hand, this feature increases the potential utility of the sample and promotes science, on the other it also enables further scientific work that may not have been specifically consented to or approved. The third challenge relates to ownership over samples, particularly in cases where cell lines are created by a biobank, and in a different country than where samples were collected. Relevant questions here concern the export of samples, approval of secondary use and the acceptability of commercialisation. A fourth challenge relates to perceptions of blood and bodily integrity, which may be particularly relevant for African research participants from certain cultures or backgrounds. Finally, we discuss challenges around informed consent and ethical review.

Summary: In this paper, we sought to map the myriad of ethical challenges that need to be considered prior to making cell line creation a reality in the H3Africa project. Considering the relative novelty of this practice in Africa, such challenges will need to be considered, discussed and potentially be resolved before cell line creation in Africa becomes financially feasible and sustainable. We suggest that discussions need to be undertaken between stakeholders internationally, considering the international character of the H3Africa project. We also map out avenues for empirical research.
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http://dx.doi.org/10.1186/1472-6939-15-60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134117PMC
August 2014

HIV-1 drug-resistance surveillance among treatment-experienced and -naïve patients after the implementation of antiretroviral therapy in Ghana.

PLoS One 2013 19;8(8):e71972. Epub 2013 Aug 19.

Department of Medical Laboratory Sciences, School of Allied Health Sciences, University of Ghana, Accra, Ghana.

Background: Limited HIV-1 drug-resistance surveillance has been carried out in Ghana since the implementation of antiretroviral therapy (ART). This study sought to provide data on the profile of HIV-1 drug resistance in ART-experienced and newly diagnosed individuals in Ghana.

Methods: Samples were collected from 101 HIV-1-infected patients (32 ART-experienced cases with virological failure and 69 newly diagnosed ART-naïve cases, including 11 children), in Koforidua, Eastern region of Ghana, from February 2009 to January 2010. The pol gene sequences were analyzed by in-house HIV-1 drug-resistance testing.

Results: The most prevalent HIV-1 subtype was CRF02_AG (66.3%, 67/101) followed by unique recombinant forms (25.7%, 26/101). Among 31 ART-experienced adults, 22 (71.0%) possessed at least one drug-resistance mutation, and 14 (45.2%) had two-class-resistance to nucleoside and non-nucleoside reverse-transcriptase inhibitors used in their first ART regimen. Importantly, the number of accumulated mutations clearly correlated with the duration of ART. The most prevalent mutation was lamivudine-resistance M184V (n = 12, 38.7%) followed by efavirenz/nevirapine-resistance K103N (n = 9, 29.0%), and zidovudine/stavudine-resistance T215Y/F (n = 6, 19.4%). Within the viral protease, the major nelfinavir-resistance mutation L90M was found in one case. No transmitted HIV-1 drug-resistance mutation was found in 59 ART-naïve adults, but K103N and G190S mutations were observed in one ART-naïve child.

Conclusions: Despite expanding accessibility to ART in Eastern Ghana, the prevalence of transmitted HIV-1 drug resistance presently appears to be low. As ART provision with limited options is scaled up nationwide in Ghana, careful monitoring of transmitted HIV-1 drug resistance is necessary.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0071972PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747072PMC
April 2014

External financial aid to blood transfusion services in sub-Saharan Africa: a need for reflection.

PLoS Med 2012 11;9(9):e1001309. Epub 2012 Sep 11.

University of Cambridge, Cambridge, United Kingdom.

Jean-Pierre Allain and colleagues argue that, while unintended, the foreign aid provided for blood transfusion services in sub-Saharan Africa has resulted in serious negative outcomes, which requires reflection and rethinking.
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http://dx.doi.org/10.1371/journal.pmed.1001309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439367PMC
February 2013

Prevalence of blood-borne infectious diseases in blood donors in Ghana.

J Clin Microbiol 2002 Sep;40(9):3523-5

Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.

Transfusion-transmissible infections among 808 blood donors in Ghana were investigated in 1999. Antibody seroprevalences of 3.8, 0.7, 8.4, and 13.5%, respectively, for human immunodeficiency virus, human T-cell lymphotrophic virus type 1, hepatitis C virus (HCV), and Treponema pallidum were obtained. The seroprevalence of HCV infection was confirmed to be 0.9% after supplementary testing, and the transfusion risk potential of these pathogens was demonstrated.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC130790PMC
http://dx.doi.org/10.1128/jcm.40.9.3523-3525.2002DOI Listing
September 2002